A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein Journal Article


Authors: Dyck, J. A.; Maul, G. G.; Miller, W. H. Jr; Chen, J. D.; Kakizuka, A.; Evans, R. M.
Article Title: A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein
Abstract: Acute promyelocytic leukemia (APL) is associated with a t(15; 17) translocation that creates the promyelocyte-retinoic acid receptor α (PML-RARα) fusion gene. Immunohistochemistry demonstrates that PML is a part of a novel macromolecular organelle (including at least three other nuclear proteins) referred to as PML oncogenic domains (PODs). In APL cells, the POD is disrupted into a microparticulate pattern as a consequence of the expression of the PML-RAR oncoprotein. RA treatment of APL cells triggers a reorganization of PML to generate normal-appearing PODs. We propose that PML-RAR is a dominant negative oncoprotein that exerts its putative leukomogenic effect by inhibiting assembly of the POD. According to this proposal, not only is the POD a novel structure, but it can be ascribed an imputed function such that its disruption leads to altered myeloid maturation; this may represent a novel oncogenic target. © 1994.
Keywords: immunohistochemistry; oncoprotein; human cell; nonhuman; animal cell; gene expression; protein assembly; neoplasm proteins; animalia; transcription factors; nuclear proteins; oncogenes; leukemia, promyelocytic, acute; fluorescent antibody technique; leukemogenesis; tumor suppressor proteins; promyelocytic leukemia; translocation, genetic; cell nucleus; cell organelle; macromolecule; macromolecular substances; chromosomes, human, pair 17; chromosomes, human, pair 15; tretinoin; receptors, retinoic acid; humans; human; priority journal; article; retinoic acid binding protein
Journal Title: Cell
Volume: 76
Issue: 2
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 1994-01-28
Start Page: 333
End Page: 343
Language: English
DOI: 10.1016/0092-8674(94)90340-9
PROVIDER: scopus
PUBMED: 8293467
DOI/URL:
Notes: Export Date: 14 January 2019 -- Article -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Wilson H. Miller Jr
    48 Miller